1. Field of the Invention
The present invention relates to the field of mass spectrometry, and more particularly the present invention relates to 2D linear multipole traps configured to enable ion/ion reactions, such as, but not limited to electron transfer dissociation.
2. Discussion of the Related Art
Mass spectrometry is one of the most common and most important tools in chemical analysis and became a key technique in the discovery of the electron and the isotopes. The analysis of organic compounds is especially challenging as such compounds cover a wide mass range from about 15 amu up to several hundred thousand amu, wherein the compounds themselves are often fragile and non-volatile.
In general, a mass spectrometer includes an ion source, a mass analyzer and some form of one or more detectors. As part of the function of the ion source, sample particles are ionized with techniques that can include chemical reactions, electrostatic forces, laser beams, electron beams, or other particle beams. The resultant ions are subsequently directed to one or more mass analyzers that separate the ions based on their mass-to-charge ratios. The separation can be temporal, e.g., in a time-of-flight analyzer, spatial e.g., in a magnetic sector analyzer, or in a frequency space, e.g., in ion cyclotron resonance (ICR) cells. The ions can also be separated according to their stability in a multipole ion trap or ion guide. The separated ions are detected by the aforementioned one or more detectors so as to provide data that enable the reconstruction of a resultant mass spectrum of the sample particles.
As part of the directing of the particles within a mass spectrometer, the ions are guided, trapped or analyzed using magnetic fields or electric potentials, or a combination of magnetic fields and electric potentials. For example, static electric fields are used in time of flight instruments and electrostatic traps, like the Orbitrap™, static magnetic and static electric fields are used in ICR cells, and static and dynamic multipole electric potentials are used in multipole traps such as, two-dimensional (2D) quadrupole traps or three-dimensional (3D) quadrupole ion traps. However, while a (3D) quadrupole ion trap, e.g., Paul trap, forms a true 3D trapping potential it has only a limited space charge capacity.
With respect to linear 2D multipole traps, such devices, which can be operated as collision cells, often include multipole electrode assemblies, such as quadrupole, hexapole, octapole or greater electrode assemblies that include four, six, eight or more rod electrodes, respectively. The rod electrodes are arranged in the assembly about an axis to define a channel in which the ions are confined in radial directions by a 2D multipole potential that is generated by applying radio frequency (“RF”) voltages to the rod electrodes. The ions are traditionally confined axially, in the direction of the channel's axis, by DC biases applied to the rod electrodes or other electrodes such as plate lens electrodes in the trap. In a portion of the channel defined by the rod electrodes, the applied DC biases can generate electrostatic potentials that axially confine in predetermined sections of the device either positive ions or negative ions, but cannot simultaneously trap both. Additional AC voltages can be applied to the rod electrodes to excite, eject, or activate some of the trapped ions.
2-D ion guides can also include a multitude of closely spaced “stacked” ring or plate electrodes having apertures that can but not necessarily decrease in size from the entrance of the device to its exit to manipulate the ions along the induced ion channel of the configuration. Detailed background information on an example stacked ring structure can be found in U.S. Pat. No. 7,514,673, entitled Ion Transport Device,” issued Apr. 7, 2009, to Senko et al. Generally described, the ring or plate electrodes are designed to have coupled oscillatory (RF) voltages with appropriate RF phase relationships to radially confine the ions. In order to provide focusing of ions to the centerline of the ion channel near the device exit, the spacing between adjacent electrodes may be increased in the direction of ion travel. The relatively greater inter-electrode spacing near the device exit provides for proportionally increased oscillatory field penetration, thereby creating a tapered field that concentrates ions to the longitudinal centerline. The magnitudes of the oscillatory voltages may be temporally varied in a scanned or stepped manner in order to optimize transmission of certain ion species or to reduce mass discrimination effects. A longitudinal DC field, which assists in propelling ions along the ion channel, may be created by applying a set of DC voltages to the electrodes.
Another exemplary type of 2D-guide comprises stacked plates or rings arranged parallel and generally transverse to the travel axis of ions (See Gerlich et al, (1992) Inhomogeneous Electrical Radio Frequency Fields: A versatile tool for the study of processes with slow ions. Adv. In Chem Phys LXXXII, 1. ISBN 0-471-53258-4, John Wiley and Sons). Generally, such structures are also arranged as radio frequency (RF) ion guides and operated under elevated pressures to efficiently transmit ions from one portion of a spectrometer to another. These devices work on the principle of so called “effective potential wells” that can trap the ions in these wells for extended periods of time either by the use of cylindrical geometry devices such as conventional Paul traps, or using linear geometry devices such as multipole guides or ring sets with end plates providing a trapping D.C. potential.
In MS/MS experiments, selected precursor ions are often first isolated or selected, and next reacted or activated to induce fragmentation to produce product ions. Mass spectra of the product ions can be measured to determine structural components of the precursor ions. Typically, the precursor ions are fragmented by collision activated dissociation (“CAD”) in which the precursor ions are kinetically excited by electric fields in an ion trap that also includes a low pressure inert gas. The excited precursor ions collide with molecules of the inert gas and may fragment into product ions due to the collisions.
In a different arrangement, product ions can be produced by electron capture dissociation (ECD) or ion/ion interactions. In ECD, low energy electrons are captured by multiply charged positive precursor ions, which then may undergo fragmentation due to the electron capture. To induce ECD processes in ICR cells, the precursor ions and the electrons are radially confined by large magnetic fields, typically from about three to about nine Tesla. Axially, the positive precursor ions and the electrons are confined by electrostatic potentials in adjacent regions. Near the border of the adjacent regions, trajectories of the precursor ions and the electrons may overlap and ECD may take place. Alternatively, the trapped precursor ions may be exposed to a flux of low energy electrons. However, ECD processes are difficult to carry out in an ion trap as the applied RF fields are not conducive for receiving low energy electrons. For example, thermal electrons, if introduced into the RF fields of a RF 3D quadrupole ion trap (QIT), a quadrupole time-of-flight (TOF), or a linear RF 2D quadrupole ion trap (QLT) instrument, maintain their thermal energies for only a fraction of a microsecond and are not trapped. Therefore, the technique remains exclusive to expensive MS instruments, such as, for example, FUR mass spectrometers.
Therefore, development of an ECD-like dissociation process for use with low cost instruments, such as a QLT, is desirable. Interestingly, electron transfer dissociation (ETD) is such a desirable alternative method for peptide dissociation by fragmenting the peptides via ion/ion chemistry using RF multipole ion trapping devices. Similar to ECD, ETD typically requires that the relative kinetic energy of the interacting particles be small, preferably less than (10, 5, 2) eV, optimally less than about 1 eV. However, ETD typically fragments the confined peptides by transferring an electron from a radical anion to a protonated peptide. This induces fragmentation of the peptide backbone, causing cleavage of the bonds just as ECD does. This creates complementary c and z-type ions instead of the typical b and y-type ions observed in CAD. Beneficially, ETD preserves post translational modifications (PTMs), such as, phosphorylations, sulfations and glycosylations that are labile by CAD and thus desirable sequence information of the peptide can be obtained.
Linear 2D multipole traps, as described above, have the desired higher capacities that can be beneficially utilized for ion/ion reactions, such as ETD, but such devices do require additional electrical fields to trap both educts simultaneously. The ion/ion reactions in linear RF multipole traps are typically induced by trapping the analytes and focusing the reactants into the trap. In such a manner, the RF pseudo potential is non-repulsive along throughout the length of the device to enable charge transfer to take place. Means of entering the trap can include parallel or perpendicular entry to the axis of the multipole. For simultaneous trapping of ions and cations, segmented traps have in the past been utilized by those skilled in the art to trap the different species in different segments with additional DC fields to predetermined segments and an added RF potential to the end lenses to enable the ion/ion reactions to take place.
To give the reader an idea of additional technical capabilities presently in the field, one is directed to background information for a system that teaches the application of a DC axial field in a RF multipole instrument, as described and claimed in U.S. Pat. No. 7,067,802, entitled, “Generation of combination of RF and axial DC electric fields in an RF-only multipole,” issued Jun. 27, 2006, to Kovtoun, including the following, “[a]n RF-only multipole includes a spiral resistive path formed around each multipole rod body. RF voltages are applied to the rod body and resistive path, and DC voltages are applied to the resistive path, to create a radially confining RF field and an axial DC field that assists in propelling ions through the multipole interior along the longitudinal axis thereof. In one implementation, the resistive path takes the form of a wire of resistive material, such as nichrome, which is laid down in the groove defined between threads formed on the rod body. The RF-only multipole of the invention avoids the need to use auxiliary rods or similar supplemental structures to generate the axial DC field.”
Background information on a system and method that confines positive and negative ions in a linear trap, is described and claimed in U.S. Pat. No. 7,145,139, entitled, “Confining Positive and Negative Ions With fast Oscillating Electrical Potentials,” to Syka, issued Dec. 5, 2006, including the following, “[m]ethods and apparatus for trapping or guiding ions. Ions are introduced into an ion trap or ion guide. The ion trap or ion guide includes a first set of electrodes and a second set of electrodes. The first set of electrodes defines a first portion of an ion channel to trap or guide the introduced ions. Periodic voltages are applied to electrodes in the first set of electrodes to generate a first oscillating electric potential that radially confines the ions in the ion channel, and periodic voltages are applied to electrodes in the second set of electrodes to generate a second oscillating electric potential that axially confines the ions in the ion channel.”
Background information on a system and method that stores ions of a first species in a linear ion trap and then subsequently transmits an oppositely charged species through the stored first species to provide for ion/ion reactions is described and claimed in U.S. Patent Application Publication No. U.S. 2008/0128611 A1, entitled, “Method and Apparatus For Transmission Mode Ion/Ion Dissociation,” to McLuckey et al., issued Published Jun. 5, 2008, including the following, “[a] method and apparatus for analyzing biomolecules is described. The method includes injecting and storing one species of ionized molecule in a linear ion trap and injecting second species of oppositely polarity ionized molecule such that the second species is transmitted through the stored first species. The resultant reaction products may be analyzed by a mass analyzer taking account of the remaining charge values. In an aspect, a linear ion trap may be used as the reaction volume, and the ionized species injected along the axis of the trap in a substantially collinear manner. The mass analysis may be performed by mass selective axial ejection or by a mass spectrometer.”
Background information that teaches electron transfer dissociation (ETD) in an ion trap, is described and claimed in U.S. Pat. No. 7,456,397, entitled, “Ion Fragmentation By Electron Transfer In Ion Traps,” issued Nov. 25, 2008, to Hartmer et al, including the following, “[t]he invention relates to a method and instrument for the fragmentation of large molecular analyte ions, preferably biopolymer ions, by reactions between multiply charged positive analyte ions and negative reactant ions in RF quadrupole ion traps. Some of these reactions involve electron transfer reactions with subsequent dissociation of the biopolymer analyte ions, and some involve the loss of a proton, leading to stable product ions. The invention can use any type of ion traps, particularly three-dimensional RF quadrupole ion traps, for the reactions between positive and negative ions. The fragmentation yield can be increased because ions that remain stable as radical cations after transfer of an electron are further fragmented by collisionally induced fragmentation, forming fragment ions that are typical of electron transfer, and not those typical of collisionally induced fragmentation. The invention preferentially introduces positive ions and negative ions into the ion trap sequentially through the same aperture.”
Additional background information that teaches electron transfer dissociation (ETD) in an ion trap, is described and claimed in U.S. Pat. No. 7,534,622 B2, entitled, “Electron Transfer Dissociation For Biopolymer Sequence Mass Spectrometer Analysis,” issued May 19, 2009, to Hunt et al, including the following, “[t]he present invention relates to a new method for fragmenting ions in a mass spectrometer through the use of electron transfer dissociation, and for performing sequence analysis of peptides and proteins by mass spectrometry. In the case of peptides, the invention promotes fragmentation along the peptide backbone and makes it possible to deduce the amino acid sequence of the sample, including modified amino acid residues, through the use of an RF field device.”
Accordingly, a need exists for improved methods and configurations to simultaneously confine precursor and reagent ions (i.e., cations and anions) within a RF field of multipole trapping devices so as to induce desired ion/ion reactions, in particular, ETD ion/ion reactions. The present invention is directed to such a need.